Vaccine cells made from bits of healthy prostate tissue DNA attack only cancerous cells, leaving healthy tissue unharmed. Human trials “within two years.”
Mayo Clinic investigators and collaborators from the UK cured well-established prostate tumors in mice using a human vaccine with no apparent side effects, as reported June 19 in Nature Medicine.
• This novel cancer treatment approach encourages the immune system to rid itself of prostate tumors without assistance from toxic chemotherapies and radiation treatments.
• Such a treatment model could some day help people to live tumor free with fewer side effects than those experienced from current therapies.
"We are hopeful that this will overcome some of the major hurdles which we have seen with immunotherapy cancer research," says Mayo Clinic immunologist Richard Vile, PhD, a lead author of the study.
(Mayo reportedly sees more prostate cancer patients than any other medical center in the world, and its Cancer Center is a leader in translation of biological research to improved methods of prevention, detection, and treatment.)
Mayo's immunotherapy research, led by Dr. Vile:
• Already shows promise in treating prostate cancer and melanoma.
• And is a prime candidate for treatment of many more aggressive cancers, such as lung, brain and pancreatic cancer.
Among the team's findings: no trace of autoimmune diseases in the mice. The murine T-cells attacked only cancerous prostate cells, leaving the healthy tissue unharmed.
To develop this new approach:
• Geneticists assembled snippets of genetic code from healthy human prostate tissue into a complementary DNA (cDNA) library.
• These bits of cDNA were then inserted into a swarm of vesicular stomatitis viruses (VSV),
• Which were cultured and reintroduced into the test mice as a vaccine during a series of intravenous injections.
Development of comprehensive cDNA libraries from healthy human prostate tissue represents the key to successful immunotherapy.
All infections, allergens and tissues, including tumors, have a unique fingerprint called an antigen - a molecular protein tag that triggers a response from the body's immune system.
Dr. Vile deployed the human vaccine prostate cancer antigens through the mutated VSV vector to raise a full-on assault from the mice's T-cells. After exposure to the mutated viruses, the animals' immune systems recognized the antigens expressed in the virus and produced a potent immune response to attack the prostate tumors.
"Nobody really knows how many antigens the immune system can really see on tumor cells," says Dr. Vile.
• "By expressing all of these proteins in highly immunogenic viruses, we increased their visibility to the immune system.
• “The immune system now thinks it is being invaded by the viruses, which are expressing cancer-related antigens that should be eliminated."
Previous attempts to vaccinate against prostate and other types of cancerous tumors have been hampered largely by researchers' inability to isolate a sufficiently diverse and robust collection of antigens in tumor cells. Because of this, tumors often mutate and re-establish themselves in spite of the body's immune system.
The use of viruses as vectors for cDNA libraries overcomes the difficulty of isolating antigens in tumor cells by giving the immune system a more complete picture of the cancerous invader.
This study was a Mayo collaboration with Alan Melcher, PhD, and Peter Selby, PhD, both from the Cancer Research UK Clinical Centre at St. James' University Hospital and professors at the Leeds Institute of Molecular Medicine, University of Leeds, UK….
The study was funded by the National Institutes of Health, Cancer Research UK, The Richard M. Schulze Family Foundation, the Mayo Clinic, and a private grant.
Source: Mayo Clinic (Rochester, MN) news release and website, Jun 19, 2011